3S2K
Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6.
Summary for 3S2K
| Entry DOI | 10.2210/pdb3s2k/pdb |
| Descriptor | Low-density lipoprotein receptor-related protein 6, Dickkopf-related protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | wnt co-receptor, beta-propeller, egf domain, wnt signaling, wnt inhibitor, glycosylation, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 157566.80 |
| Authors | Ahn, V.E.,Chu, M.L.-H.,Choi, H.-J.,Tran, D.,Abo, A.,Weis, W.I. (deposition date: 2011-05-16, release date: 2011-11-02, Last modification date: 2024-11-06) |
| Primary citation | Ahn, V.E.,Chu, M.L.,Choi, H.J.,Tran, D.,Abo, A.,Weis, W.I. Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6. Dev.Cell, 21:862-873, 2011 Cited by PubMed Abstract: LDL receptor-related proteins 5 and 6 (LRP5/6) are coreceptors for Wnt growth factors, and also bind Dkk proteins, secreted inhibitors of Wnt signaling. The LRP5/6 ectodomain contains four β-propeller/EGF-like domain repeats. The first two repeats, LRP6(1-2), bind to several Wnt variants, whereas LRP6(3-4) binds other Wnts. We present the crystal structure of the Dkk1 C-terminal domain bound to LRP6(3-4), and show that the Dkk1 N-terminal domain binds to LRP6(1-2), demonstrating that a single Dkk1 molecule can bind to both portions of the LRP6 ectodomain and thereby inhibit different Wnts. Small-angle X-ray scattering analysis of LRP6(1-4) bound to a noninhibitory antibody fragment or to full-length Dkk1 shows that in both cases the ectodomain adopts a curved conformation that places the first three repeats at a similar height relative to the membrane. Thus, Wnts bound to either portion of the LRP6 ectodomain likely bear a similar spatial relationship to Frizzled coreceptors. PubMed: 22000856DOI: 10.1016/j.devcel.2011.09.003 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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